3-Methyl-1-phenyl-2-pyrazolin-5-one is a cerebral protective agent which has a free radical eliminating function and is used with an injectable solution (intravenous drip infusion; intravenous injection by drip) as an improving drug for neurological syndromes, impairment of daily living activities, and functional impairment in humans accompanied by cerebral infarction acute period. Recently, many people are suffering from cerebral dysfunction brought on by aging, variation in diet, an increase in stress in daily life, and the like, and as a result, quick and precise countermeasures for cerebral dysfunction are now an important issue in medicine.
Free radicals such as hydroxy radicals (—OH) which are produced in excess in the body during ischemia due to cerebral infarction or the like and after restoration of blood flow thereafter result in a chain reaction of oxygenation damage in cell membranes in humans, thereby further worsening cerebral ischemia damage. In this case, if an injectable solution containing 3-methyl-1-phenyl-2-pyrazolin-5-one (trade name: Radicut Injection 30 mg; injectable solution including 30 mg of active ingredient per dose) is used through intravenous drip infusion, the injectable solution demonstrates excellent treatment effects against cerebral ischemia damage by eliminating the hydroxy radicals in the bodies of humans.
The injectable solution, however, causes a patient pain due to the fact that an injection needle punctures the body (vein) of the patient during intravenous drip infusion of the injectable solution. Further, the intravenous drip infusion is normally performed on a patient who is lying down on a bed, which means the patient is restricted to the bed for a certain period of tie (i.e., while the intravenous drip infusion is being performed). In addition, with the exception of some injectable solutions such as insulin and interferon, injections are not able to be administered by the patient him/herself. An intravenous drip infusion of the injectable solution containing 3-methyl-1-phenyl-2-pyrazolin-5-one is also obviously not able to be administered by the patient him/herself, which means that (administration of) the intravenous drip infusion must be done by a doctor, a female nurse, or a male nurse. As a result, the patient is compelled to be admitted into a hospital or go to a hospital for the intravenous drip infusion. Even if the patient is admitted into a hospital or goes to a hospital for the intravenous drip infusion, the patient feels pain during the intravenous drip infusion, and a healthcare practitioner such as a doctor, female nurse, or male nurse must take the time to perform (administer) the intravenous drip infusion. As a result, if the intravenous drip infusion is administered twice daily according to the dosage regimen, for example, each time it causes the patient pain and takes the time of a healthcare practitioner.
Also, side-effects such as impaired liver function are being reported following intravenous drip infusion of the injectable solution. A temporary increase in the concentration of medication in the blood from the intravenous drip infusion can easily be assumed to be one cause. Given these circumstances, development of a preparation containing 3-methyl-1-phenyl-2-pyrazolin-5-one which is easy to administer, which has lasting effects over an extended period of time, and which has few side-effects is required.
When 3-methyl-1-phenyl-2-pyrazolin-5-one is used as an agent to normalize brain function, methods of administration as an injectable solution, an oral agent, or a suppository (administered rectally) are disclosed in Japanese Patent Application Laid-Open No. 61-263917, for example, but only an injectable solution is currently used in clinical practice. One reason for this is because many disorders that the agent to normalize brain function is aimed to treat occur following cerebral infarction, so many patients to whom the agent to normalize brain function is administered are incapacitated or unconscious which makes it difficult to administer the agent orally. In addition, many of the patients to whom the agent to normalize brain function is administered are elderly patients who fundamentally have a difficult time taking medication orally.
Furthermore, 3-methyl-1-phenyl-2-pyrazolin-5-one is quickly metabolized in the liver by glucuronate conjugation or sulfate conjugation so the effectiveness from the first passage effect in the liver is extremely low when administered orally. Also, 3-methyl-1-phenyl-2-pyrazolin-5-one is disclosed as a lipid peroxide production inhibiting agent (see Japanese Patent Application Laid-Open No. 62-108814, for example), an antiulcer agent (see Japanese Patent Application Laid-Open No. 3-215425, for example), an anti-hyperglycenic agent (see Japanese Patent Application Laid-Open No. 3-215426, for example), an agent for ocular disease (see Japanese Patent Application Laid-Open No. 7-25765, for example), an agent for treating/preventing acute hepatic failure (see Japanese Patent Application Laid-Open No. 9-52831, for example), and the like. All of these agents, however, are administered orally, intravenously, or rectally and thus have the drawbacks described above in clinical practice.